Excitotoxicity is a pathological process in which neurons are damaged or killed due to the excessive stimulation of certain neurotransmitters such as glutamate. This process of excitotoxic neuronal death is known to contribute to the pathogenesis of brain and/or spinal cord injury associated with multiple human diseases such as Amyotrophic lateral sclerosis (ALS). (2) ALS is a progressive neurodegenerative disease that involves both the upper and lower motor neurons. Glutamate excitotoxicity is one of three major pathophysiological mechanisms of motor neuron injury where current research is being focused on regarding ALS. (1)
Glutamate excitotoxicity occurs when receptors for glutamate such as the NMDA receptor and AMPA receptor are overactivated …show more content…
In classical acute excitotoxicity, there is influx of sodium and chlorine ions and destabilization of intracellular calcium levels, which activates a cascade of harmful biochemical events. 2
Glutamate is produced through the cell’s metabolic processes and it contains 4 major receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. NMDA and kainic acid activate glutamate receptors and can cause classical acute excitotoxicity.
The destabilization of intracellular calcium levels activates a number of enzymes such as: phospholipases, endonucleases, and proteases. These enzymes are capable of damaging cell structures such as components of the cytoskeleton, cell membrane and DNA. This eventually leads to apoptosis of the cell. 7
The concept of secondary excitotoxicity, where cellular injury by glutamate is triggered by disturbances in neuronal energy status, may be particularly relevant to a chronic neurodegenerative disease such as ALS. …show more content…
3 Two important molecular features of motor neurons have been recognized as contributes to the vulnerability of neurodegeneration. The low expression of calcium binding proteins and the low expression of the GluR2 AMPA receptor subunit by weak motor neuron groups makes them highly susceptible to calcium-mediated toxic events following glutamate receptor activation. 2
As a treatment for ALS, Riluzole is a drug that is currently used. It works by blocking the release of glutamate and it has been shown to extend survival in ALS patients by about two months. Riluzole has been known to be a moderately safe drug. 5 However, Riluzole is not a cure for ALS, it is used purely as a treatment to prolong the patient’s life. 4 Riluzole works by blocking the release of glutamate, therefor the amount of motor neurons committing apoptosis decreases.
However, glutamate is the major excitatory neurotransmitter in the brain and the blockage of it completely might have an effect on the CNS. A primary function of glutamate is to get neurons fired up. It stimulates them so they can perform important functions like learning new information or forming memories. If glutamate was to be completely blocked off, more damage is being added on to the patient’s system along with them having progressive
Glutamate excitotoxicity occurs when receptors for glutamate such as the NMDA receptor and AMPA receptor are overactivated …show more content…
In classical acute excitotoxicity, there is influx of sodium and chlorine ions and destabilization of intracellular calcium levels, which activates a cascade of harmful biochemical events. 2
Glutamate is produced through the cell’s metabolic processes and it contains 4 major receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. NMDA and kainic acid activate glutamate receptors and can cause classical acute excitotoxicity.
The destabilization of intracellular calcium levels activates a number of enzymes such as: phospholipases, endonucleases, and proteases. These enzymes are capable of damaging cell structures such as components of the cytoskeleton, cell membrane and DNA. This eventually leads to apoptosis of the cell. 7
The concept of secondary excitotoxicity, where cellular injury by glutamate is triggered by disturbances in neuronal energy status, may be particularly relevant to a chronic neurodegenerative disease such as ALS. …show more content…
3 Two important molecular features of motor neurons have been recognized as contributes to the vulnerability of neurodegeneration. The low expression of calcium binding proteins and the low expression of the GluR2 AMPA receptor subunit by weak motor neuron groups makes them highly susceptible to calcium-mediated toxic events following glutamate receptor activation. 2
As a treatment for ALS, Riluzole is a drug that is currently used. It works by blocking the release of glutamate and it has been shown to extend survival in ALS patients by about two months. Riluzole has been known to be a moderately safe drug. 5 However, Riluzole is not a cure for ALS, it is used purely as a treatment to prolong the patient’s life. 4 Riluzole works by blocking the release of glutamate, therefor the amount of motor neurons committing apoptosis decreases.
However, glutamate is the major excitatory neurotransmitter in the brain and the blockage of it completely might have an effect on the CNS. A primary function of glutamate is to get neurons fired up. It stimulates them so they can perform important functions like learning new information or forming memories. If glutamate was to be completely blocked off, more damage is being added on to the patient’s system along with them having progressive